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| 2. |
- Woldmar, N., et al.
(författare)
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Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases
- 2023
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Brain metastases are associated with considerable negative effects on patients’ outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases. Materials and methods: Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259. Results: Out of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases. Conclusions: This is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.
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| 4. |
- Trinh, Xuan Thang, et al.
(författare)
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Identification of the negative carbon vacancy at quasi-cubic site in 4H-SiC by EPR and theoretical calculations
- 2014
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Ingår i: Silicon Carbide and Related Materials 2013, PTS 1 AND 2. - : Trans Tech Publications Inc.. ; , s. 285-288
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Konferensbidrag (refereegranskat)abstract
- In freestanding n-type 4H-SiC epilayers irradiated with low-energy (250 keV) electrons at room temperature, the electron paramagnetic resonance (EPR) spectrum of the negative carbon vacancy at the hexagonal site, V-C(-)(h), and a new signal were observed. From the similarity in defect formation and the spin-Hamiltonian parameters of the two defects, the new center is suggested to be the negative C vacancy at the quasi-cubic site, V-C(-)(k). The identification is further supported by hyperfine calculations.
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| 5. |
- Trinh, Xuan Thang, et al.
(författare)
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Negative-U carbon vacancy in 4H-SiC : Assessment of charge correction schemes and identification of the negative carbon vacancy at the quasicubic site
- 2013
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 88:23, s. 235209-1-235209-13
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Tidskriftsartikel (refereegranskat)abstract
- The carbon vacancy (VC) has been suggested by different studies to be involved in the Z1/Z2 defect-a carrier lifetime killer in SiC. However, the correlation between the Z1/Z2 deep level with VC is not possible since only the negative carbon vacancy (V−C) at the hexagonal site, V−C(h), with unclear negative-U behaviors was identified by electron paramagnetic resonance (EPR). Using freestanding n-type 4H-SiC epilayers irradiated with low energy (250 keV) electrons at room temperature to introduce mainly VC and defects in the C sublattice, we observed the strong EPR signals of V−C(h) and another S = 1/2 center. Electron paramagnetic resonance experiments show a negative-U behavior of the two centers and their similar symmetry lowering from C3v to C1h at low temperatures. Comparing the 29Si and 13C ligand hyperfine constants observed by EPR and first principles calculations, the new center is identified as V−C(k). The negative-U behavior is further confirmed by large scale density functional theory supercell calculations using different charge correction schemes. The results support the identification of the lifetime limiting Z1/Z2 defect to be related to acceptor states of the carbon vacancy.
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| 7. |
- Agoston, EI, et al.
(författare)
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Deconstructing Immune Cell Infiltration in Human Colorectal Cancer: A Systematic Spatiotemporal Evaluation
- 2022
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Cancer-related immunity has been identified as playing a key role in the outcome of colorectal cancer (CRC); however, the exact mechanisms are only partially understood. In this study, we evaluated a total of 242 surgical specimen of CRC patients using tissue microarrays and immunohistochemistry to evaluate tumor infiltrating immune cells (CD3, CD4, CD8, CD20, CD23, CD45 and CD56) and immune checkpoint markers (CTLA-4, PD-L1, PD-1) in systematically selected tumor regions and their corresponding lymph nodes, as well as in liver metastases. Additionally, an immune panel gene expression assay was performed on 12 primary tumors and 12 consecutive liver metastases. A higher number of natural killer cells and more mature B cells along with PD-1+ expressing cells were observed in the main tumor area as compared to metastases. A higher number of metastatic lymph nodes were associated with significantly lower B cell counts. With more advanced lymph node metastatic status, higher leukocyte—particularly T cell numbers—were observed. Eleven differentially expressed immune-related genes were found between primary tumors and liver metastases. Also, alterations of the innate immune response and the tumor necrosis factor superfamily pathways had been identified.
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| 8. |
- Almeida, Natália, et al.
(författare)
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Mapping the melanoma plasma proteome (MPP) using single-shot proteomics interfaced with the WiMT database
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:24
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Tidskriftsartikel (refereegranskat)abstract
- Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom protein databases for ID generation. This entails a multi-level dynamic protein database with different immunodepletion strategies by applying single-shot proteomics. The highest number of melanoma plasma proteins from undepleted and unfractionated plasma was reported, mapping >1200 proteins from >10,000 protein sequences with confirmed significance scoring. Of these, more than 660 proteins were annotated by WiMT from the resulting ~5800 protein sequences. We could verify 4000 proteins by MS1t analysis from HeLA extracts. The WiMT platform provided an output in which 12 previously well-known candidate markers were identified. We also identified low-abundant proteins with functions related to (i) cell signaling, (ii) immune system regulators, and (iii) proteins regulating folding, sorting, and degradation, as well as (iv) vesicular transport proteins. WiMT holds the potential for use in large-scale screening studies with simple sample preparation, and can lead to the discovery of novel proteins with key melanoma disease functions.
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| 9. |
- Antonini, Angelo, et al.
(författare)
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Levodopa-carbidopa intestinal gel in advanced Parkinson's : Final results of the GLORIA registry
- 2017
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 45, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care. Methods: Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39. Results: Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in "Off" time (hours/day) (mean ± SD = -4.1 ± 3.5, P < 0.001), "On" time with dyskinesia (hours/day) (-1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (-7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%). Conclusions: LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.
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| 10. |
- Kero, Johan, et al.
(författare)
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A meteor head echo analysis algorithm for the lower VHF band
- 2012
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Ingår i: Annales Geophysicae. - Gottingen : Copernicus Gesellschaft mbH. - 0992-7689 .- 1432-0576. ; 30:4, s. 639-659
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Tidskriftsartikel (refereegranskat)abstract
- We have developed an automated analysis scheme for meteor head echo observations by the 46.5 MHz Middle and Upper atmosphere (MU) radar near Shigaraki, Japan (34.85A degrees N, 136.10A degrees E). The analysis procedure computes meteoroid range, velocity and deceleration as functions of time with unprecedented accuracy and precision. This is crucial for estimations of meteoroid mass and orbital parameters as well as investigations of the meteoroid-atmosphere interaction processes. In this paper we present this analysis procedure in detail. The algorithms use a combination of single-pulse-Doppler, time-of-flight and pulse-to-pulse phase correlation measurements to determine the radial velocity to within a few tens of metres per second with 3.12 ms time resolution. Equivalently, the precision improvement is at least a factor of 20 compared to previous single-pulse measurements. Such a precision reveals that the deceleration increases significantly during the intense part of a meteoroid's ablation process in the atmosphere. From each received pulse, the target range is determined to within a few tens of meters, or the order of a few hundredths of the 900 m long range gates. This is achieved by transmitting a 13-bit Barker code oversampled by a factor of two at reception and using a novel range interpolation technique. The meteoroid velocity vector is determined from the estimated radial velocity by carefully taking the location of the meteor target and the angle from its trajectory to the radar beam into account. The latter is determined from target range and bore axis offset. We have identified and solved the signal processing issue giving rise to the peculiar signature in signal to noise ratio plots reported by Galindo et al. (2011), and show how to use the range interpolation technique to differentiate the effect of signal processing from physical processes.
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